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IL-33 controls IL-22-dependent antibacterial defense by modulating the microbiota.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 May 28; Vol. 121 (22), pp. e2310864121. Date of Electronic Publication: 2024 May 23. - Publication Year :
- 2024
-
Abstract
- IL-22 plays a critical role in defending against mucosal infections, but how IL-22 production is regulated is incompletely understood. Here, we show that mice lacking IL-33 or its receptor ST2 (IL-1RL1) were more resistant to Streptococcus pneumoniae lung infection than wild-type animals and that single-nucleotide polymorphisms in IL33 and IL1RL1 were associated with pneumococcal pneumonia in humans. The effect of IL-33 on S. pneumoniae infection was mediated by negative regulation of IL-22 production in innate lymphoid cells (ILCs) but independent of ILC2s as well as IL-4 and IL-13 signaling. Moreover, IL-33's influence on IL-22-dependent antibacterial defense was dependent on housing conditions of the mice and mediated by IL-33's modulatory effect on the gut microbiota. Collectively, we provide insight into the bidirectional crosstalk between the innate immune system and the microbiota. We conclude that both genetic and environmental factors influence the gut microbiota, thereby impacting the efficacy of antibacterial immune defense and susceptibility to pneumonia.<br />Competing Interests: Competing interests statement:The authors declare no competing interest.
- Subjects :
- Animals
Mice
Humans
Mice, Knockout
Microbiota immunology
Mice, Inbred C57BL
Pneumonia, Pneumococcal immunology
Pneumonia, Pneumococcal microbiology
Gastrointestinal Microbiome immunology
Lymphocytes immunology
Lymphocytes metabolism
Polymorphism, Single Nucleotide
Interleukin-33 immunology
Interleukin-33 genetics
Interleukin-33 metabolism
Interleukins metabolism
Interleukins immunology
Interleukins genetics
Interleukin-22
Streptococcus pneumoniae immunology
Immunity, Innate
Interleukin-1 Receptor-Like 1 Protein metabolism
Interleukin-1 Receptor-Like 1 Protein genetics
Interleukin-1 Receptor-Like 1 Protein immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 121
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 38781213
- Full Text :
- https://doi.org/10.1073/pnas.2310864121